Functional Connectivity as a Potential Mechanism for Language Plasticity.

Abstract

Task fMRI is a clinical tool for language lateralization, but has limitations, and cannot provide information about network-level plasticity. Additional methods are needed to improve the precision of presurgical language mapping. We investigate language resting-state functional connectivity (RS fMRI; FC) in typically developing children (TD) and children with epilepsy. Our objectives were to (1) understand how FC components differ between TD children and those with epilepsy; (2) elucidate how the location of disease (frontal/temporal epilepsy foci) affects FC; and (3) investigate the relationship between age and FC. Our sample included 55 TD children (mean age 12 years, range 7-18) and 31 patients with focal epilepsy (mean age 13 years, range 7-18). All participants underwent RS fMRI. Using a bilateral canonical language map as target, vertex-wise intrahemispheric FC map and interhemispheric FC map for each participant were computed and thresholded at top 10% to compute an FC laterality index (FCLI; [(L - R)/(L + R)]) of the frontal and temporal regions for both integration (intrahemispheric FC; FCLIi) and segregation (interhemispheric FC; FCLIs) maps. We found FC differences in the developing language network based on disease, seizure foci location, and age. Frontal and temporal FCLIi was different between groups (t[84] = 2.82, p < 0.01; t[84] = 4.68, p < 0.01, respectively). Frontal epilepsy foci had the largest differences from TD (Cohen d frontal FCLIi = 0.84, FCLIs = 0.51; temporal FCLIi = 1.29). Development and disease have opposing influences on the laterality of FC based on groups. In the frontal foci group, FCLIi decreased with age (r = -0.42), whereas in the temporal foci group, FCLIi increased with age (r = 0.40). Within the epilepsy group, increases in right frontal integration FCLI relates to increased right frontal task activation in our mostly left language dominant group (r = 0.52, p < 0.01). Language network connectivity is associated with higher verbal intelligence in children with epilepsy (r = 0.45, p < 0.05). These findings lend preliminary evidence that FC reflects network plasticity in the form of adaptation and compensation, or the ability to recruit support and reallocate resources within and outside of the traditional network to compensate for disease. FC expands on task-based fMRI and provides complementary and potentially useful information about the language network that is not captured using task-based fMRI alone.